isocyanatocyclopropane

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 30 μl (24.3 mg, 0.29 mmol) of cyclopropylisocyanate are dissolved in dichloromethan, 80.0 mg (0.146 mmol) of the compound of Example 12 are added and the mixture is stirred over night at room temperature. For the work-up the solvent is removed completely and after fine purification by preparative RP-HPLC (Method 6) 55 mg of the target compound are obtained. For the work-up the solvent is removed completely after fine purification by preparative RP-HPLC (Method 6) 55 mg of the target compound are obtained

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 30 μl (24.3 mg, 0.29 mmol) of cyclopropylisocyanate are dissolved in dichloromethan, 80.0 mg (0.146 mmol) of the compound of Example 12 are added and the mixture is stirred over night at room temperature. For the work-up the solvent is removed completely and after fine purification by preparative RP-HPLC (Method 6) 55 mg of the target compound are obtained. For the work-up the solvent is removed completely after fine purification by preparative RP-HPLC (Method 6) 55 mg of the target compound are obtained

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Cyclopropylisocyanate (4 g, 0.048 mmol) was added to a solution of 3-(1H-benzo[d]imidazol-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-amine (15 mg, 0.045 mmol) and pyridine (0.01 mL, 0.126 mmol) in CH2Cl2 (5 mL). The mixture was stirred for 24 h, and then the solvent was removed in vacuo. Purification by flash chromatography (2% CH3OH/CH2Cl2) afforded the title compound (10 mg) as a solid. 1H NMR (400 MHz, CDCl3): δ 8.22 (s, 1H), 7.93 (d, 1H, J=8.8 Hz), 7.83 (m, 1H), 7.49 (d, 1H, J=8.8 Hz), 7.27-7.24 (m, 2H), 7.17 (s, 1H), 5.71 (dd, 1H, J=2.4 and 9.2 Hz), 4.04 (m, 1H), 3785 (m, 1H), 2.59 (m, 2H), 2.17-2.07 (m, 2H), 1.74 (m, 5H), 0.84 (q, 2H, J=5.2 Hz). the solvent was removed in vacuo Purification by flash chromatography (2% CH3OH/CH2Cl2)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Tetrahydro-1-(5-methoxy-1,3,4-thiadiazol-2-yl)-3-ethyl-6-hydroxy-2(1H)-pyrimidinone (0.05 mole) and cyclopropyl isocyanate (3.5 ml; 0.07 mole) are charged into a glass reaction vessel equipped with a mechanical stirrer. The mixture is stirred and triethylamine (1 drop) is added thereto. After the addition is completed the reaction mixture is allowed to stand for a period of about 1 hour. The mixture is then washed with hexane and is dried to yield the desired product tetrahydro-1-(5-methoxy-1,3,4-thiadiazol-2-yl)-3-ethyl-6-(N-cyclopropylcarbamoyloxy)-2(1H)-pyrimidinone. equipped with a mechanical stirrer After the addition The mixture is then washed with hexane is dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Tetrahydro-1-(5-methoxy-1,3,4-thiadiazol-2-yl)-3-ethyl-6-hydroxy-2(1H)-pyrimidinone (0.05 mole) and cyclopropyl isocyanate (3.5 ml; 0.07 mole) are charged into a glass reaction vessel equipped with a mechanical stirrer. The mixture is stirred and triethylamine (1 drop) is added thereto. After the addition is completed the reaction mixture is allowed to stand for a period of about 1 hour. The mixture is then washed with hexane and is dried to yield the desired product tetrahydro-1-(5-methoxy-1,3,4-thiadiazol-2-yl)-3-ethyl-6-(N-cyclopropylcarbamoyloxy)-2(1H)-pyrimidinone. equipped with a mechanical stirrer After the addition The mixture is then washed with hexane is dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-(2,2-Dipropoxyethylthio)phenol (0.05 mole) dissolved in benzene (10 ml) is charged into a glass reaction flask equipped with a mechanical stirrer. Cyclopropylisocyanate (0.06 mole) and triethylamine (3 drops) are then added, and the resulting mixture is stirred at room temperature for a period of about 6 hours. The mixture is then stripped of solvent and unreacted isocyanate to yield the desired product O-[4-(2,2-dipropoxyethylthio)phenyl] N-cyclopropylcarbamate as the residue. is charged into a glass reaction flask equipped with a mechanical stirrer

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 108 mg (0.22 mmol) of 1-(cyclopentylcarbonyl)-5-(4-ethylphenyl)piperidine-3-amine trifluoroacetate (Example 7A) and 22 mg (0.26 mmol, 1.2 eq.) of cyclopropyl isocyanate were reacted according to General Method 4. Yield: 64 mg (76% of theory)